Cyclic AMP-responsive element modulator (CREM) is a transcription factor highly expressed in the post-meiotic germ cells of the testis. Its pivotal role is to regulate the expression of several germ cell-specific genes, a crucial function as demonstrated by the severe phenotype of mice whose CREM gene was mutated by homologous recombination. CREM-deficient male animals are sterile and display a ten-fold increase in the apoptosis of germ cells. Recent results have shown that CREM needs a tissue-specific co-activator, ACT (activator of CREM in testis) to elicit its regulatory function in testis (PMID: 10824972). Also, CREM is a crucial regulator of NK cell function. CREM exerts its regulatory functions through epigenetic reprogramming of CAR-NK cells.

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